1. Field of the Invention
The invention describes a novel method for producing [preparing] optically active 3-hydroxy- or 3,4-dihydroxypyrrolidines. The invention is relative in particular to a method of producing optically active pyrrolidines with high enantiomeric purity with the general formula ##STR2## in which R.sup.1 can be hydrogen or a hydroxy group, R.sup.2 is a benzyl group whose aromatic group can have one or more alkyl, alkoxy and/or halogen substituents and * is an asymmetric center, when the carbon atom so characterized carries a hydroxy group, by means of the reduction of enantiomerically pure 2,5 pyrrolidinediones of the general formula ##STR3## in which R.sup.1, R.sup.2 and * have the meanings indicated for formula (III).
2. Description of Related Art
These compounds are important intermediates in the chemical industry. Thus, enantiomers of 3-hydroxypyrrolidine, which are obtained from compounds of formula III (R.sup.1 =H) by catalytic hydrogenation, are structural elements in the synthesis of carbapenem antibiotics (Chemotherapy 1991, 39 (suppl. 3), 83 ff.; Tetrahedron Lett. 1984, 25 (26), 2793; JP 04036282 A2, Feb. 6, 1992; JP 03275685 A2, 12-6-91; Korean J. Med. Chem. 1993, 3 (1), 72). Enantiomers of 1-benzyl-3,4-dihydroxypyrrolidine are used in the synthesis of optically active phosphanes which serve as ligands of metallic catalysts for asymmetric hydrogenations (Chem. Ber. 1986, 119, 3326; DE 34 46 303 A1, Jun. 19, 1986; DE 34 03 194 A1, Aug. 1, 1985; Bull. Chem Soc. Jpn. 1984, 57 (3), 823).
Various methods have been described for the production of these compounds. Thus, optically active 3-hydroxypyrrolidines have been obtained by means of classic (JP 05279326 A2, Oct. 26, 1993; JP 05279325 A2, Oct.26, 1993; JP 05032620, Feb. 9, 1993; JP 04164066 A2, Jun. 9, 1992; JP 04013659 A2, Jan. 17, 1992; JP 61063652 A2, Apr. 1, 1986) or enzymatic racemate splitting (JP 05227991 A2, Sep. 7, 1993; JP 04131093 A2, May 1, 1992; JP 01141600 A2, Jun. 2, 1989). A disadvantage of these methods is the fact that the maximum yield is only 50% if the undesired enantiomer can not be returned [restored] by a racemization.
Another possibility is the decarboxylation of optically active hydroxyproline (JP 05255204 A2, Oct. 5, 1993; Bioorg. Med. Chem. Lett. 1992, 2 (8), 827; Chem. Lett. 1986 (6) 893; JP 60023328 A2, Feb. 5, 1985). This is problematic in as far as the suitable, optically active hydroxyproline is an expensive initial material which is often not available in large amounts.
Further methods are based on the cyclization of suitable butane or butyric-acid derivatives which must then, if necessary, be further converted chemically (EP 452143 A2, Oct. 16, 1991; EP 431521 A1, Jun. 12, 1991; EP 347818 A2, Dec. 27, 1989; JP 01045360 A2, Feb. 17, 1989; EP 269258 A2, Jun. 1, 1988). Syntheses starting from L-glutamic acid (Synth. Comm. 1986, 16 (14), 1815) and N-substituted 3-pyrrolines (J. Org. Chem. 1986, 51 (22), 4296) are also known. These methods require a comparatively expensive chemistry or start from precursors which are not readily obtainable.
Optically active malic and tartaric acids are very well-suited educts which are readily and inexpensively available in large amounts. They can be cyclized with benzyl amine relatively easily to the corresponding imides, which can then be reduced to the optically active hydroxy pyrrolidines and optionally be debenzylated hydrogenolytically. However, a danger thereby is the described cyclization of tartaric acid with benzyl amine in xylene since the imide formed thereby crystallizes out toward the end of the reaction "under vigorous boiling up" (Chem. Ber. 1986, 119, 3327). The reduction of the imides to the hydroxypyrrolidines is easy in principle but in the past it could only be carried out with comparatively expensive reagents which are at times problematic as concerns the safety engineering or for reasons of environmental protection, e.g. sodium boron hydride boron trifluoride etherate (Chem. Ber. 1986, 119, 3327), sodium aluminum hydride (JP 03200762 A2, Sep. 2, 1991), Na[AlH.sub.2 (OCH.sub.2 CH.sub.2 OMe).sub.2 ] (JP 01254657 A2, Oct. 11, 1989) or lithium aluminum hydride (JP 01207266 A2, Aug. 21, 1989).
Considering the state of the art presented herein, the invention has the problem of making available a further method for the production of compounds of the initially cited type which permits the obtention of the desired, optically active pyrrolidines in high enantiomeric purity using readily and inexpensively obtainable educts and which at the same time can be carried out with the least expense possible.
These and other problems which are not cited in detail are solved by means of a method of the initially mentioned type with the features of the characterizing part of claim 1.